1exv

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{{STRUCTURE_1exv| PDB=1exv | SCENE= }}
 
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===HUMAN LIVER GLYCOGEN PHOSPHORYLASE A COMPLEXED WITH GLCNAC AND CP-403,700===
 
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{{ABSTRACT_PUBMED_10980448}}
 
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==Disease==
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==HUMAN LIVER GLYCOGEN PHOSPHORYLASE A COMPLEXED WITH GLCNAC AND CP-403,700==
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[[http://www.uniprot.org/uniprot/PYGL_HUMAN PYGL_HUMAN]] Defects in PYGL are the cause of glycogen storage disease type 6 (GSD6) [MIM:[http://omim.org/entry/232700 232700]]. A metabolic disorder characterized by mild to moderate hypoglycemia, mild ketosis, growth retardation, and prominent hepatomegaly. Heart and skeletal muscle are not affected.<ref>PMID:9529348</ref>
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<StructureSection load='1exv' size='340' side='right'caption='[[1exv]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1exv]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EXV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1EXV FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=700:[5-CHLORO-1H-INDOL-2-CARBONYL-PHENYLALANINYL]-AZETIDINE-3-CARBOXYLIC+ACID'>700</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=NBG:1-N-ACETYL-BETA-D-GLUCOSAMINE'>NBG</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1exv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1exv OCA], [https://pdbe.org/1exv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1exv RCSB], [https://www.ebi.ac.uk/pdbsum/1exv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1exv ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/PYGL_HUMAN PYGL_HUMAN] Defects in PYGL are the cause of glycogen storage disease type 6 (GSD6) [MIM:[https://omim.org/entry/232700 232700]. A metabolic disorder characterized by mild to moderate hypoglycemia, mild ketosis, growth retardation, and prominent hepatomegaly. Heart and skeletal muscle are not affected.<ref>PMID:9529348</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/PYGL_HUMAN PYGL_HUMAN] Phosphorylase is an important allosteric enzyme in carbohydrate metabolism. Enzymes from different sources differ in their regulatory mechanisms and in their natural substrates. However, all known phosphorylases share catalytic and structural properties.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ex/1exv_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1exv ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Background: Glycogen phosphorylases catalyze the breakdown of glycogen to glucose-1-phosphate for glycolysis. Maintaining control of blood glucose levels is critical in minimizing the debilitating effects of diabetes, making liver glycogen phosphorylase a potential therapeutic target.Results: The binding site in human liver glycogen phosphorylase (HLGP) for a class of promising antidiabetic agents was identified crystallographically. The site is novel and functions allosterically by stabilizing the inactive conformation of HLGP. The initial view of the complex revealed key structural information and inspired the design of a new class of inhibitors which bind with nanomolar affinity and whose crystal structure is also described. Conclusions: We have identified the binding site of a new class of allosteric HLGP inhibitors. The crystal structure revealed the details of inhibitor binding, led to the design of a new class of compounds, and should accelerate efforts to develop therapeutically relevant molecules for the treatment of diabetes.
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==Function==
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Human liver glycogen phosphorylase inhibitors bind at a new allosteric site.,Rath VL, Ammirati M, Danley DE, Ekstrom JL, Gibbs EM, Hynes TR, Mathiowetz AM, McPherson RK, Olson TV, Treadway JL, Hoover DJ Chem Biol. 2000 Sep;7(9):677-82. PMID:10980448<ref>PMID:10980448</ref>
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[[http://www.uniprot.org/uniprot/PYGL_HUMAN PYGL_HUMAN]] Phosphorylase is an important allosteric enzyme in carbohydrate metabolism. Enzymes from different sources differ in their regulatory mechanisms and in their natural substrates. However, all known phosphorylases share catalytic and structural properties.
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[1exv]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EXV OCA].
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</div>
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<div class="pdbe-citations 1exv" style="background-color:#fffaf0;"></div>
==See Also==
==See Also==
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*[[Glycogen Phosphorylase|Glycogen Phosphorylase]]
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*[[Glycogen phosphorylase 3D structures|Glycogen phosphorylase 3D structures]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:010980448</ref><ref group="xtra">PMID:018434170</ref><references group="xtra"/><references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Phosphorylase]]
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[[Category: Large Structures]]
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[[Category: Ammirati, M.]]
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[[Category: Ammirati M]]
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[[Category: Danley, D E.]]
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[[Category: Danley DE]]
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[[Category: Ekstrom, J L.]]
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[[Category: Ekstrom JL]]
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[[Category: Hoover, D J.]]
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[[Category: Hoover DJ]]
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[[Category: Hynes, T R.]]
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[[Category: Hynes TR]]
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[[Category: Olson, T V.]]
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[[Category: Olson TV]]
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[[Category: Rath, V L.]]
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[[Category: Rath VL]]
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[[Category: Allosteric binding]]
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[[Category: Allosteric site]]
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[[Category: Transferase]]
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Current revision

HUMAN LIVER GLYCOGEN PHOSPHORYLASE A COMPLEXED WITH GLCNAC AND CP-403,700

PDB ID 1exv

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